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![The mechanism of colistin resistance in Enterobacter için kapak resmi The mechanism of colistin resistance in Enterobacter için kapak resmi](/client/assets/d79c3e4af2b6d196/ctx/images/no_image.png)
The mechanism of colistin resistance in Enterobacter
Başlık:
The mechanism of colistin resistance in Enterobacter
Yazar:
Chavda, Bhakti, author.
ISBN:
9780438079007
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (59 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Barry N. Kreiswirth.
Özet:
Similar to emergence and epidemic spread of carbapenem resistance in Klebsiella pneumoniae and Enterobacter spp. in NY-NJ region, colistin resistance among members of Enterobacteriaceae, particularly Enterobacter spp., have been identified in clinical settings, posing a major infection control and therapeutic challenge. In this study, we genetically characterized 23 colistin-resistant Enterobacter isolates from the US and China to explore whether the spread of colistin resistance in Enterobacter is associated with a major genetic clone. In silico MLST analysis of target genes revealed that isolates belonged to 16 different sequence types (ST), depicting the spread of colistin resistance in diverse Enterobacter genetic backgrounds. Phylogenomic analysis placed all 23 of these genomes and 83 Enterobacter genomes sequenced previously in lab into 11 phylogenomic groups. The 23 colistin resistant Enterobacter isolates from this study segregated into eight phylogenomic groups. Resistance to colistin depends on an intricate mechanism involving mutations in several genes participating in bacterial cell membrane modeling. The extensive genetic analysis of mutations in pmrA/pmrB, phoP/phoQ, ccrA/ccrB in 23 colistin resistant Enterobacter strains compared to 80 colistin susceptible strains identified numerous unique mutations that we suspect to contribute to colistin resistance. Sequence analysis of mgrB, negative regulator of phoP/phoQ, revealed genetic alterations such as nonsense mutations in three strains leading to premature termination of MgrB transmembrane protein and revealed the truncation of mgrB gene by Tn 3 family transposons. In addition to chromosomal mutations, it has been shown that acquisition of plasmid encoded mcr gene which encodes a phosphoethanolamine transferase correlates with colistin resistance. We completely sequenced and characterized three plasmids harboring mcr-4.4 gene on a ColE plasmid from clinical ST54 and ST84 Enterobacter isolates. The work presented here identifies the diverse mechanisms for colistin resistance, and improves our understanding of the factors that contribute to colistin resistance in Enterobacter spp. The findings in this thesis provide a solid genomic framework that will serve as an important resource in future development of molecular diagnostics, and in supporting drug discovery programs.
Notlar:
School code: 0198
Konu Başlığı:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(696243.1) | 696243-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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